Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Daulby Street, Liverpool L69 3GA, United Kingdom.
Vaccine. 2012 Apr 27;30 Suppl 1(0 1):A36-43. doi: 10.1016/j.vaccine.2011.09.120.
Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3-8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3-14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (vaccine efficacy 38.1% (9.8-57.3)). The point estimate of efficacy in the second year of life (17.6%; -59.2 to 56.0) was lower than in the first year of life (49.4%; 19.2-68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged to the G1P[8] genotype. While the optimal dosing schedule of RIX4414 in African infants requires further investigation, vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life.
轮状病毒胃肠炎是导致非洲婴幼儿发病和死亡的主要原因之一。在马拉维和南非开展的一项针对 G1P[8]人轮状病毒活疫苗（RIX4414）的 III 期、安慰剂对照、多中心临床试验表明，该疫苗可显著降低婴幼儿第一年严重轮状病毒胃肠炎的发病率。我们现在报告在马拉维队列儿童中进行的第二年疫苗疗效。在马拉维的布兰太尔，共有 1773 名健康婴儿被分为三组。两组分别在 6、10 和 14 周龄时接受 RIX4414 或安慰剂 3 剂，第三组在 6 周龄时接受安慰剂，在 10 和 14 周龄时接受 RIX4414。通过每周对肠胃炎发作进行家庭访视来对受试者进行随访，直至 1 岁，然后再次同意进行 18-24 个月的随访。根据 Vesikari 评分系统对肠胃炎发作的严重程度进行分级。通过 ELISA 法检测疫苗前和疫苗后的血样，对部分儿童进行了抗轮状病毒 IgA 的血清转化检测。通过 RT-PCR 法确定轮状病毒 VP7（G）和 VP4（P）基因型。在整个随访期间，与安慰剂组相比，接受 2 剂和 3 剂 RIX4414 组的 1030 名受试者中共有 70/1030（6.8%，95%CI 5.3-8.5）出现严重轮状病毒胃肠炎，而安慰剂组 483 名受试者中共有 53/483（11.0%，8.3-14.1）出现严重轮状病毒胃肠炎（疫苗效力为 38.1%（9.8-57.3））。第二年的疗效点估计（17.6%；-59.2 至 56.0）低于第一年（49.4%；19.2-68.3）。与接受两剂方案相比，接受三剂方案的儿童第二年的疗效呈升高趋势，三剂 RIX4414 组的抗轮状病毒 IgA 血清应答率更高，但差异无统计学意义。检测到的轮状病毒株包括基因型 G12（31%）；G9（23%）；G8（18%）；只有 18%的株属于 G1P[8]基因型。虽然 RIX4414 在非洲婴儿中的最佳剂量方案仍需进一步研究，但在感染轮状病毒负担高的贫困非洲人群中，接种 RIX4414 可显著降低由多种轮状病毒株引起的严重胃肠炎的发病率。
